This paper investigates the determinants of TFP for Italian regions. We find strong evidence in favour of the factors commonly suggested by the theoretical literature. In particular, R&D expenditures and the number of researchers are positively related to regional TFP. Moreover, human capital is an important determinant of TFP. Finally, we find a strong difference between Northern and Southern regions, particularly regarding the effect of research activity and social capital. Our results are robust across different estimation methods.